High-Dose Firmonertinib Plus Bevacizumab as Neoadjuvant Therapy for Resectable EGFRm Stage II-IIIB NSCLC

High-dose Firmonertinib Combined With Bevacizumab as Neoadjuvant Therapy in Stage II-IIIB, Resectable, EGFR-mutated Non-small Cell Lung Cancer Patients: A Single-arm, Multi-center, Open-label Phase II Clinical Study

This is a Phase II, single-arm, open-label, multicenter clinical study aimed at evaluating the efficacy and safety of Firmonertinib 160 mg combined with Bevacizumab as neoadjuvant therapy in patients with resectable stage II-IIIB Epidermal Growth Factor Receptor(EGFR)-mutated non-small cell lung cancer.

Inclusion Criteria:

1. Male or female, aged ≥18 years.
2. Histologically/cytologically confirmed primary non-small cell lung cancer within 60 days prior to the study.
3. Stage II-IIIB disease evaluated by endobronchial ultrasound guided tranbronchial needle aspiration(EBUS-TBNA), mediastinoscopy, or Positron Emission Tomography/Computed Tomography (PET/CT), with lesions planned for radical resection after neoadjuvant therapy.
4. EGFR mutation-positive confirmed by local laboratory testing of tissue or blood samples.
5. Presence of at least one measurable lesion, with a baseline Computed Tomography (CT) scan showing the longest diameter ≥10 mm (except for lymph nodes, which must have a short axis ≥15 mm), and suitable for accurate repeated measurements.
6. ECOG performance status score of 0-1, with no deterioration within 2 weeks prior to the first dose administration.
7. Female patients should adopt fully effective contraceptive measures, must not be breastfeeding, and have a negative pregnancy test before the first administration of the study drug; or female patients must meet the following criteria at screening to confirm the absence of reproductive potential:
8. Postmenopausal, defined as age greater than 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormonal therapies.
9. For women under 50 years of age, they are considered postmenopausal if they have not had a menstrual period for 12 months or more after stopping exogenous hormone therapy, and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the postmenopausal range.
10. Documented irreversible sterilization procedures, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, excluding tubal ligation.
11. Male patients should be willing to use barrier contraception, i.e., condoms.

Exclusion Criteria:

1. Presence of small cell lung cancer or mixed pathological types of NSCLC. EGFR exon 20 insertion mutation detected by genetic testing.

2. Exposure to any other antitumor therapy prior to enrollment, including perioperative radiotherapy.

3. The patient is in pregnancy or lactation.

4. History of other malignant tumors, or currently combined with other malignant tumors (except for malignancies that have undergone radical surgery with no recurrence within 5 years post-operation, such as cervical carcinoma in situ, basal cell carcinoma of the skin, and papillary thyroid carcinoma, etc.).

5. Presence of severe or uncontrolled systemic diseases requiring treatment, which the investigator deems unsuitable for trial participation, including hypertension, diabetes mellitus, chronic heart failure (New York Heart Association, NYHA Class III-IV), unstable angina, myocardial infarction within the past year, etc.

6. Severe gastrointestinal dysfunction, diseases, or clinical conditions that may affect the intake, transport, or absorption of the study drug, such as inability to take oral medications, uncontrollable nausea and vomiting, extensive gastrointestinal resection history, etc.

7. Any of the following laboratory tests indicate insufficient bone marrow reserve or organ reserve function.

   • Absolute neutrophil count <1.5×10^9/L
   • Platelet count <100×10^9/L
   • Hemoglobin <90 g/L
   • Alanine aminotransferase (ALT) >2.5×upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) >2.5×ULN
   • Total bilirubin >1.5×ULN or >3×ULN in cases of Gilbert's syndrome (unconjugated hyperbilirubinemia)

8. Known or suspected allergy to almonertinib mesylate, bevacizumab, or any other component of their formulations, or patients with other contraindications.

9. If the patient cannot comply with the study procedures, restrictions, and requirements, or if the investigator deems the patient ineligible or unsuitable for participation in the study for any other reason.

10. Patients currently or previously enrolled in any other anti-tumor clinical studies.